Search results for "KINASE"

Nueva era en el combate contra el cáncer: Evolución y cáncer: progreso y tratamiento de tumores

2013

L’oncohematologia ha assistit en les últimes dècades a importants avenços en el tractament i supervivència. La toxicitat derivada de la quimioteràpia clàssica i la necessitat de millorar l’eficàcia i tolerància als tractaments han fet que es desencadene un allau d’activitat investigadora que constantment proporciona fruits. Gran part d’aquest esforç s’ha enfocat al desenvolupament de «teràpies diana» dirigides contra determinades alteracions funcionals, clau per a la supervivència de la cèl·lula tumoral. Així es pretén aconseguir major eficàcia en el tractament i que el pacient pague un menor cost en toxicitat. Avenços en altres disciplines de l’oncologia com l’epidemiologia, la cirurgia i …

V gamma 9V delta 2 T lymphocytes efficiently recognize and kill zoledronate-sensitized, imatinib-sensitive, and imatinib-resistant chronic myelogenou…

2010

Abstract Imatinib mesylate (imatinib), a competitive inhibitor of the BCR-ABL tyrosine kinase, is highly effective against chronic myelogenous leukemia (CML) cells. However, because 20–30% of patients affected by CML display either primary or secondary resistance to imatinib, intentional activation of Vγ9Vδ2 T cells by phosphoantigens or by agents that cause their accumulation within cells, such as zoledronate, may represent a promising strategy for the design of a novel and highly innovative immunotherapy capable to overcome imatinib resistance. In this study, we show that Vγ9Vδ2 T lymphocytes recognize, trogocytose, and efficiently kill imatinib-sensitive and -resistant CML cell lines pre…

The closure of Pak1-dependent macropinosomes requires the phosphorylation of CtBP1/BARS

2007

Membrane fission is an essential process in membrane trafficking and other cellular functions. While many fissioning and trafficking steps are mediated by the large GTPase dynamin, some fission events are dynamin independent and involve C-terminal-binding protein-1/brefeldinA-ADP ribosylated substrate (CtBP1/BARS). To gain an insight into the molecular mechanisms of CtBP1/BARS in fission, we have studied the role of this protein in macropinocytosis, a dynamin-independent endocytic pathway that can be synchronously activated by growth factors. Here, we show that upon activation of the epidermal growth factor receptor, CtBP1/BARS is (a) translocated to the macropinocytic cup and its surroundi…

Light-dependent CK2-mediated phosphorylation of centrins regulates complex formation with visual G-protein.

2008

AbstractCentrins are Ca2+-binding EF-hand proteins. All four known centrin isoforms are expressed in the ciliary apparatus of photoreceptor cells. Cen1p and Cen2p bind to the visual G-protein transducin in a strictly Ca2+-dependent way, which is thought to regulate light driven movements of transducin between photoreceptor cell compartments. These relatively slow motile processes represent a novel paradigm in light adaptation of photoreceptor cells.Here we validated specific phosphorylation as a novel regulator of centrins in photoreceptors. Centrins were differentially phosphorylated during photoreceptor dark adaptation. Inhibitor treatments revealed protein kinase CK2 as the major protein…

Optomotor-blind negatively regulates Drosophila eye development by blocking Jak/STAT signaling

2015

Organ formation requires a delicate balance of positive and negative regulators. In Drosophila eye development, wingless (wg) is expressed at the lateral margins of the eye disc and serves to block retinal development. The T-box gene optomotor-blind (omb) is expressed in a similar pattern and is regulated by Wg. Omb mediates part of Wg activity in blocking eye development. Omb exerts its function primarily by blocking cell proliferation. These effects occur predominantly in the ventral margin. Our results suggest that the primary effect of Omb is the blocking of Jak/STAT signaling by repressing transcription of upd which encodes the Jak receptor ligand Unpaired.

Angiopoietin-2 plasma dosage predicts time to first treatment and overall survival in chronic lymphocytic leukemia.

2010

Abstract The clinical relevance of angiopoietin-2 (Ang2) in chronic lymphocytic leukemia (CLL) was previously suggested by the association between high Ang2, and shorter progression-free survival reported in small series of patients. Here, we evaluated Ang2 glycoprotein levels in plasma samples collected from a multicentric cohort of CLL patients (n = 316) using an enzyme-linked immunosorbent assay method, and we investigated its prognostic role in relation to time to first treatment (TTFT) and overall survival. Based on a cutoff equal to 2459 pg/mL, we divided our cohort in 2 subsets (high and low Ang2) composing 100 (31.6%) and 216 (68.4%) patients, respectively. High Ang2 was predictive …

Possible mechanisms of Raf-1 Kinase Inhibitor Protein down-regulation in hepatocellular carcinoma

2011

Induction of Apoptosis and Chemosensitization by the Histone Deacetylase Inhibitor Trichostatin in Hepatocellular Carcinoma Cells: Molecular Analysis…

2011

The mRNA and protein levels of RKIP are reduced and those of YY1 increased in clinical HCC. Loss, mutation, or promoter hypermethylation of the RKIP gene may not account for the downregulation of RKIP in HCC. Histone deacetylation can silence gene expression and play a significant role in hepatocarcinogenesis. The histone deacetylase inhibitor (HDACI) trichostatin induced cell growth inhibition and proapoptotic effects in HA22T/VGH and HepG2 HCC cells; it also exhibited synergy with doxorubicin. Treatment with trichostatin caused histone hyperacetylation and down- or upregulated expression of different genes (such as β-catenin, cyclin D1, hTERT, XIAP, and IL-6). These changes might, at leas…

The grapevine LysM receptor-like kinase VvLYK5-1 mediates chitin-triggered immunity

2021

The establishment of defense reactions to protect plants against invading pathogens first requiresthe recognition of Microbe-Associated Molecular Patterns (MAMPs), detected by plasmamembrane-bound Pattern Recognition Receptors (PRRs). These MAMPs, also termed elicitors, areused in several biocontrol products that are gradually developing to reduce the use of chemicalpesticides in agriculture. Chitin, the main component of fungal cell walls, as well as its deacetylatedderivative, chitosan, are two chitooligosaccharides (COS) that can be found in some of theseproducts. Unfortunately, the mechanism allowing the perception of these molecules is still poorlyunderstood in Vitis vinifera, sometime…

A non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease

2018

Endothelial nitric oxide (NO) stimulates the heme protein, soluble guanylyl cyclase (sGC) to form vasoprotective cyclic GMP (cGMP). In different disease states such as pulmonary hypertension, NO-cGMP signaling is pharmacologically augmented, yet the pathomechanisms leading to its dysregulation are incompletely understood. Here we show in pulmonary artery endothelial cells that endogenous NO or NO donor compounds acutely stimulate sGC activity, but chronically down-regulate both sGC protein and cGMP formation. Surprisingly, this endogenous feedback mechanism was independent of canonical cGMP signaling via cGMP-dependent protein kinase. It did not involve thiol-dependent modulation, a process…